Abstract

Background

Sipuleucel-T is an autologous cellular immunotherapy approved by the US FDA for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). In the Phase 3 mCRPC trials, APC activation in the sipuleucel-T product correlated with overall survival. In this analysis, sipuleucel-T product characteristics were compared across a range of disease states.

Baseline demographics were generally representative of each disease state: patients in the neoadjuvant setting were younger with lower disease burden; those with mCRPC had the highest disease burden and more patients had received prior chemotherapy. APC activation patterns were similar among trials, with increased CD54 upregulation at the second and third treatment. The median cumulative fold increase in CD54 upregulation in patients with earlier disease (neoadjuvant: 35.5, serological progression: 43.5) was significantly greater than in patients with asymptomatic or minimally symptomatic mCRPC (28.7) and mCRPC (21.8) (p < 0.0001). During sipuleucel-T manufacture, lymphocyte activation and cytokine profiles were similar across disease states, with consistently enhanced expression at the second and third doses.

Conclusion

The process of manufacturing sipuleucel-T activates APCs in both early and late disease states, and generates similar T and B cell activation and cytokine profiles consistent with immunological prime-boost. However, APC activation was more robust in earlier disease states, raising the possibility that patients with less advanced disease may derive greater benefit.